This proposal is for 5 years of funding for a NIAMS Career Development Award, through the mechanism of the Mentored Research Scientist Development Award (K01) program. The goal of the training award is to develop the candidate's knowledge and skills in epidemiologic methods, data analysis and interpretation, as well as to provide her with a solid understanding of clinical rheumatology in terms of disease manifestations, treatment and treatment outcomes, to complement the expertise that she has already gathered in the genetics of rheumatoid arthritis (RA), leading to her transition to being able to independently conduct genetic epidemiology studies. The career development plan will develop the candidate's skills in 1) epidemiology methods and applications to complex disease research, 2) clinical rheumatology, and 3) application of epidemiology methods to genetic data within the context of gene association studies. Methods of career development include 1) the proposed study, 2) the mentorship of Drs. Nelson Freimer, Lindsey Criswell and Jorn Olsen, 3) consultation with experts in clinical rheumatology, and observation at rheumatology clinics, 4) formal coursework in epidemiology, leading to a Masters in Epidemiology, 5) attendance at scientific meetings, 6) data preparation for submission of manuscripts to peer-reviewed journals, and preparation of R01 grant application using preliminary data generated from this career development award. The main objective of the research plan is to examine gender differences in disease features, responses to treatment, and associations with candidate gene markers among RA patients, using epidemiological methods. These aims will test the hypothesis that male RA patients, in particular those with younger age at onset, have a higher load of genetic and non-genetic risk factors for the disease, and hence have more severe disease manifestations and possibly different responses to treatment. A better understanding of the sex differences in RA might provide clues about underlying disease mechanisms and could also have an important impact on RA prognosis and therapy. With the proposed mentorship, outstanding resources, research environment and the candidate's prior training, a K01 award will facilitate the candidate's transition to becoming an independent researcher in the field of rheumatic disease genetics.